Human endometrial receptivity is a critical determinant of pregnancy success; however, in vivo studies of its features and regulation are particularly challenging due to ethical restrictions. Recently, the development of human endometrial assembloids has provided a powerful model to investigate this intricate biological process. In this study, we established a specialized human window-of-implantation (WOI) endometrial assembloid system that mimics the in vivo receptive endometrium. It not only reproduces the structural attributes of pinopodes and cilia, but also molecular characteristics of mid-secretory endometrium. Furthermore, the WOI endometrial assembloid exhibits hormone responsiveness, an energy metabolism profile characterized by larger and functionally enhanced mitochondria, increased ciliary assembly and motility, and epithelial-mesenchymal transition (EMT), as well as promising potential for embryo implantation. As such, WOI assembloids hold great promise as a platform to unravel the intricate mechanisms governing the regulation of endometrial receptivity, maternal-fetal interactions, and associated pathologies, ultimately driving impactful advancements in the field.

Embryo-maternal interaction is essential for post-implantation human development. While endometrial organoids have enabled in vitro modeling of the uterine environment, a fully integrated 3D co-culture system with human embryos has not been established. Here, we develop a physiologically relevant 3D platform that supports the co-culture of human embryos with endometrial organoids, enabling reciprocal embryo-maternal communication. This system sustains development to day 14 post-fertilization with structural and molecular fidelity to Carnegie stage landmarks, including yolk sac formation, primordial germ cell specification, and trophoblast maturation. Single-cell transcriptomics and functional assays reveal that the endometrial niche accelerates extravillous trophoblast emergence at day 9 post-fertilization and primes their invasive programs. Disruption of maternal signals, including human chorionic gonadotropin signaling blockade, markedly impairs embryonic progression. This co-culture system provides a powerful and tractable model to dissect human peri- and post-implantation development, with broad relevance to early pregnancy loss, placental biology, and reproductive medicine.

BACKGROUND:Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously. CASE PRESENTATION:We report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment. CONCLUSIONS:This is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians' understanding of this disease for early detection, diagnosis and treatment.

INTRODUCTION:The pathogenesis of pelvic organ prolapse (POP), an age-related disease, has not been fully elucidated. Therapeutic targets of POP are limited. Silencing information regulator 2 related enzyme 1 (SIRT1), a gene considered capable of regulating oxidative stress and cellular senescence, has been widely demonstrated involved in aging and age-related diseases. The present study aimed to explore the role of SIRT1 in POP in vivo and in vitro.METHODS:Expression levels of SIRT1 in uterosacral ligament (USL) tissues from patients with or without POP were measured using immunohistochemical assays. SRT1720, a SIRT1 agonist, was used to upregulate SIRT1, and hydrogen peroxide (H2O2) was used to establish an oxidative stress model in human uterosacral ligament fibroblasts (hUSLFs). The effects of SIRT1 on cell viability, apoptosis, senescence, and reactive oxygen species (ROS) levels were detected, respectively. Western blot assays were used to examine expression levels of apoptosis- and senescence-associated biomarkers. Unpaired Student's t test, Mann-Whitney U test, χ2 test, and one-way ANOVA were performed for determining statistically significant differences.RESULTS:Compared to the control group, expression levels of SIRT1 were downregulated in USL tissues and hUSLFs from patients with POP, and associated with stage (p < 0.05). hUSLFs of patients with POP had lower growth rates (p < 0.0001) than those of the control group, which were improved by upregulating SIRT1 (p < 0.05). The senescent proportion was higher in the POP group than the control group (43.63 ± 10.62% vs. 4.84 ± 5.32%, p < 0.0001), which could be reduced by upregulating SIRT1 (p < 0.0001). High ROS levels in the POP group were also alleviated by SRT1720. H2O2 exposure increased ROS levels, inhibited proliferation, and triggered apoptosis and senescence in hUSLFs of patients without POP in a concentration-dependent manner. Further, these damages were alleviated by pretreatment with SRT1720.CONCLUSIONS:SIRT1 is downregulated in patients with POP, and the development of SIRT1 activators or agonists may have applications in the treatment and prevention of POP through antioxidative stress and antisenescence effects.

Research question: What influence does an intramural myoma have on the endometrium, and how is this mediated? Design: Endometrium was collected from 13 patients with non-cavity-distorting intramural myomas (diameter <4 cm; International Federation of Gynecology and Obstetrics type 4) and 13 patients without myomas undergoing hysterectomy for benign cervical diseases with a similar clinical baseline. Endometrial organoids were established in vitro and induced to reach the secretory phase by oestrogen and progesterone. Transcriptome sequencing was conducted on endometrial organoids in both untreated and secretory stages from three individuals with myomas and three control participants. Immunofluorescence and real-time quantitative PCR (RT-qPCR) were performed on endometrial organoids from another 10 myoma patients and 10 control patients for validation. Results: The data revealed abnormally increased hormone receptor (PGR) levels in the untreated endometrial organoids with myomas, resulting in potentially abnormal glandular and vascular development. The aberrant responses to oestrogen and progestogen prompted further investigation into the secretory phase. The secretory endometrial organoids with myomas. Conclusions: This study is thefirst to reveal that intramural myomas create an abnormal hormonal and mechanical environment in the untreated and secretory endometrial organoids. The intramural myomas negatively impacted gene expression relating to endometrial glands, blood vessels, cilia and ECM, indicating that intramural myomas impair endometrial decidualization and receptivity

OBJECTIVE:To investigate the pro-apoptotic effects of Indirubin, a traditional Chinese medicine, on ovarian cancer SKOV3 cell line and to explore its underlying mechanisms. METHODS:Ovarian cancer SKOV3 cells were divided into a control group (cells cultured normally) and an experimental group (cells cultured in medium containing Indirubin). SKOV3 cells at the logarithmic phase were treated with Indirubin at various concentrations. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, while apoptosis was detected by flow cytometry, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunofluorescence. Transcriptome sequencing was conducted to screen for apoptosis-related factors. qPCR and western blot were used to detect the mRNA and protein expression on added of molecules related to mitochondrial permeability transition pores. RESULTS:MTT assay showed that Indirubin inhibited the growth of SKOV3 cells in both plate and sphere cultures, with IC50 values of 3.003 μM (plate culture) and 4.253 μM (sphere culture), respectively. Indirubin showed a lower inhibitory concentration than cisplatin (IC50 3.687 μM in plate culture and 7.023 μM in sphere culture), and its effect was comparable to adriamycin. Flow cytometry revealed an increase in apoptosis rates in SKOV3 cells treated with Indirubin. Transcriptome sequencing indicated significant changes in the transcription of various apoptosis-related genes, particularly those involved in the mitochondrial apoptosis pathway, such as Bcl-2-associated X protein (Bax) and Bcl2 associated agonist of cell death (Bad). After Indirubin treatment, the mRNA and protein expression levels of mitochondrial channel-related genes Cyclophilin D (CyPD), adenine nucleotide translocator 1 (ANT1), and voltage-dependent anion channel (VADC) were significantly elevated (all P < 0.05). By regulating the mitochondrial membrane permeability through the Bcl-2 family members, Indirubin promoted apoptosis in SKOV3 cells. CONCLUSION:Indirubin inhibits the proliferation and promotes the apoptosis of ovarian cancer cells, exerting an anti-tumor effect. Its pro-apoptotic action is closely related to the mitochondrial apoptosis pathway.

Low grade endometrial stromal sarcoma (LG-ESS) is a rare malignancy of mesenchymal origin in the female reproductive system, which has the characteristic of late recurrence. Endometrial carcinoma is a group of epithelial tumors, and is one of the most common gynecological malignancies among women worldwide. The coexistence of LG-ESS and endometrial carcinoma is extremely rare, and there is no relevant report about the collision of endometrial carcinoma and recurrent LG-ESS currently. In the present study, we report a tumor of recurrent LG-ESS accompanied with endometrioid adenocarcinoma in a young patient 8 years after hysterectomy. She was first diagnosed with LG-ESS at the age of 19 and received fertility-sparing therapy. During the 13-year follow-up period, she successfully delivered and experienced two recurrences of LG-ESS, and an unexpected endometrioid adenocarcinoma component was found in the second recurrent tumor. Adjuvant chemotherapy and endocrine therapy were administrated to the patient after completely removing the tumor, and no sign of disease recurrence or metastasis were found 7 months after the last surgery. This study emphasizes the importance of long-term management of LG-ESS and brings new insights to clinicians and pathologists about collision tumors involving recurrent tumor.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13048-020-00723-7.

目的 分析诺舒(NovaSure)子宫内膜消融技术(EA)治疗异常子宫出血(AUB)的临床意义、效果及远期预后.方法 回顾性分析2015-2017年山东大学齐鲁医院85例采用NovaSure系统进行子宫内膜消融术的患者,采用图形失血量评估表(PBLAC)测定月经失血量,视觉模拟评分法(VAS)评估痛经程度,并应用SPSS 21.0软件对所有数据进行分析.结果 在85例接受治疗的妇女中,69例有完整的随访信息,其中51例患者术后闭经(73.9％51/69);15例患者术后出血量明显减少(24.6％15/69).术后月经量PBLAC评分、痛经程度VAS评分与术前相比均明显下降,差异有统计学意义(P＜0.05).结论 NovaSure子宫内膜消融术是一种安全、有效的治疗异常子宫出血的方法,可有效缓解痛经、减少月经量,且手术时间短,术中出血量少,便于操作,尤其适用于合并严重内科疾病的患者.

Background Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC. Methods Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays. Results Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4. Conclusions PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

Purpose: Nutritional and inflammatory states are crucial in cancer development. The purpose of this study is to construct a scoring system grounded on peripheral blood parameters associated with nutrition and inflammation and explore its value in stage, overall survival (OS), and progression-free survival (PFS) prediction for epithelial ovarian cancer (EOC) patients.Patients and Methods: Four hundred and fifty-three EOC patients were retrospectively identified and their clinical data and relevant peripheral blood parameters were collected. The ratio of neutrophil to lymphocyte, lymphocyte to monocyte, fibrinogen to lymphocyte, total cholesterol to lymphocyte and albumin level were calculated and dichotomized. A scoring system named peripheral blood score (PBS) was constructed. Univariate and multivariate Logistic or Cox regression analyses were used to select independent factors; these factors were then used to develop nomogram models of advanced stage and OS, PFS, respectively. The internal validation and DCA analysis were performed to evaluate models.Results: Lower PBS indicated a better prognosis and higher PBS indicated inferior. High PBS is associated with advanced stage, high CA125, serous histological type, poor differentiation, and accompanied ascites. The logistic regression showed age, CA125, and PBS were independent factors for the FIGO III-IV stage. The nomogram models for advanced FIGO stage based on these factors showed good efficiency. FIGO stage, residual disease, and PBS were independent factors affecting OS and PFS, the nomogram models composed of these factors had good performance. DCA curves revealed the models augmented net benefits.Conclusion: PBS can be a noninvasive biomarker for EOC patients' prognosis. The related nomogram models could be powerful, cost-effective tools to provide information of advanced stage, OS, and PFS for EOC patients.

微管功能的多样性受到翻译后修饰(PTM)的影响,其中通过去除α-微管蛋白末端的酪氨酸所产生的去酪氨酸化修饰作用在妇科肿瘤转移中发挥着重要作用.近来,微管蛋白羧肽酶(TCP)的鉴定引起了人们对这一修饰作用的广泛关注.本文综述了微管蛋白去酪氨酸化修饰的过程及功能,探讨了该修饰对妇科肿瘤转移和微管靶向药物治疗的影响,为妇科肿瘤靶向治疗提供新的思路.

Vasohibin1 (VASH1) is a kind of vasopressor, produced by negative feedback from vascular endothelial growth factor A (VEGFA). Anti-angiogenic therapy targeting VEGFA is currently the first-line treatment for advanced ovarian cancer (OC), but there are still many adverse effects. Regulatory T cells (Tregs) are the main lymphocytes mediating immune escape function in the tumor microenvironment (TME) and have been reported to influence the function of VEGFA. However, whether Tregs are associated with VASH1 and angiogenesis in TME in OC is unclear. We aimed to explore the relationship between angiogenesis and immunosuppression in the TME of OC. We validated the relationship between VEGFA, VASH1, and angiogenesis in ovarian cancer and their prognostic implications. The infiltration level of Tregs and its marker forkhead box protein 3 (FOXP3) were explored in relation to angiogenesis-related molecules. The results showed that VEGFA and VASH1 were associated with clinicopathological stage, microvessel density and poor prognosis of ovarian cancer. Both VEGFA and VASH1 expression were associated with angiogenic pathways and there was a positive correlation between VEGFA and VASH1 expression. Tregs correlated with angiogenesis-related molecules and indicated that high FOXP3 expression is harmful to the prognosis. Gene set enrichment analysis (GSEA) predicted that angiogenesis, IL6/JAK/STAT3 signaling, PI3K/AKT/mTOR signaling, TGF-β signaling, and TNF-α signaling via NF-κB may be common pathways for VEGFA, VASH1, and Tregs to be involved in the development of OC. These findings suggest that Tregs may be involved in the regulation of tumor angiogenesis through VEGFA and VASH1, providing new ideas for synergistic anti-angiogenic therapy and immunotherapy in OC.

Pelvic organ prolapse (POP) is a conventional gynecological condition and the mechanism is not entirely clear. Although an increasing number of studies revealed that long non-coding RNAs (lncRNAs) have essential functions in many diseases, little knowledge has been acquired in POP. The current study aimed to investigate the regulatory mechanism of lncRNA in POP. In this report, we investigated the expression profile of lncRNAs and mRNAs between POP and the control groups in human uterosacral ligament (hUSL) tissues through RNA-seq. Cytoscape was used to construct a POP-specific lncRNA-mRNA network and select key molecules. This RNA-Seq analysis uncovered a total of 289 lncRNAs, and 41 lncRNAs and 808 mRNAs were differentially expressed between the POP and non-POP groups. Four lncRNAs were identified and validated by real-time PCR. The result of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) indicated that differentially expressed lncRNAs were abundant in the biological processes and signaling pathways concerned in POP. The differentially expressed lncRNAs were mainly enriched in protein binding, the single-organism cellular process, and cytoplasmic part. The network was constructed based on the correlation analyses of the abnormally expressed lncRNAs and their target proteins to imitate their interactions. Taken together, this study was the first to demonstrate the differential expression profiles of lncRNA in POP and normal tissues by sequencing technology. Our study indicated that lncRNAs could correlate with the development of POP and may be as significant genes in the diagnosis and treatment of POP.

系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种慢性自身免疫性疾病,具有不同的临床表型,主要影响育龄期的妇女[1 ].患有SLE 的孕妇会增加流产、早产、低出生体质量和先兆子痫的风险[2].已有多份关于SLE 伴有子宫收缩乏力和子宫肌层极薄的病例,有些患者同时被诊断为胎盘植入.一项研究结果表明,SLE 患者在接受免疫抑制剂(如糖皮质激素)治疗时可能出现类固醇生成缺陷[3],抑制子宫内雌激素受体和减少蛋白质合成而加剧子宫肌层萎缩[4-5].胎盘植入因蜕膜发育不良和滋养层细胞异常侵入可能导致分娩时出血[6 ].羟氯喹常被用于治疗SLE ,但有报道称其与蜕膜发育不良有关[7].然而,没有明确的证据显示SLE与子宫肌层变薄和胎盘植入之间的关系.本研究通过分析 1 例 SLE 孕妇子宫肌层弥漫性明显变薄并伴有胎盘植入患者的资料,并与既往文献进行比较,以提高对此类疾病的认识.

Aims: To assess the difference in survival between fertility-sparing surgery (FSS) and radical surgery and explore pregnancy outcomes after FSS in stage I malignant sex cord-stromal tumours (MSCSTs). Materials and methods: We carried out a multicentre retrospective cohort study on patients who were diagnosed with MSCSTs and the tumour was confined to one ovary. The patients were divided into FSS and radical surgery groups. Inverse probability of treatment weighting (IPTW) was used to balance variables between the two groups. Kaplan-Meier analysis was used to compare the difference in disease-free survival (DFS). Univariate and multivariate Cox regression analysis was used to find risk factors of DFS. Univariate logistic regression analysis was used to assess risk factors of pregnancy. Results: In total, 107 patients were included, of whom 54 (50.5%) women underwent FSS and 53 (49.5%) received radical surgery. After IPTW, a pseudo -population of 208 was determined and all of the covariates were well balanced. After a median follow-up time of 50 months (range 7-156 months), 10 pa-tients experienced recurrence and two died. There was no significant difference in DFS between the two groups, both in unweighted (P 1/4 0.969) or weighted cohorts (P 1/4 0.792). In the weighted cohort, stage IC (P 1/4 0.014), tumour diameter >8 cm (P 1/4 0.003), incomplete staging surgery (P 1/4 0.003) and no adjuvant chemotherapy (P < 0.001) were the four high-risk factors associated with a shorter DFS. Among 14 patients who had pregnancy desire, 11 (78.6%) women conceived successfully; the live birth rate was 76.9%. In univariate analysis, only adjuvant chemotherapy (P 1/4 0.009) was associated with infertility. Conclusions: On the premise of complete staging surgery, FSS is safe and feasible in early stage MSCSTs with satisfactory reproductive outcomes. (c) 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

1 临床资料 患者,女,31岁,孕3产1,既往无异常妊娠史.妊娠14周时因超声发现胎儿脐带底部两个囊性肿块就诊于山东大学齐鲁医院产科门诊,行超声检查示:胎儿脐带底部向腹外膨出一大小约2.9 cm×2.7 cm×2.6 cm的囊性肿块,直接与膀胱相连,位于两条脐动脉之间,肿块和膀胱连接处形成沙漏状外观.腹外可见一大小约5.1 cm×3.4 cm×3.6 cm的囊性肿块(图1A).超声诊断:胎儿脐带囊肿和脐尿管未闭.

Background Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Efficacy of the bromodomain 4 (BRD4) inhibitor JQ1 has been reported for the treatment of various human cancers, but its potential impact on EC remains unclear. We therefore aimed to elucidate the function of BRD4 and the effects of JQ1 in EC in vivo and in vitro. Methods The mRNA expression of BRD4 was evaluated using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). BRD4 protein expression in EC tissues was measured using immunohistochemistry (IHC) assays. The effects of JQ1 on EC were determined by using MTT and colony formation assays, flow cytometry and xenograft mouse models. The underlying mechanism was also examined by western blot and small interfering RNA (siRNA) transfection. Results BRD4 was overexpressed in EC tissues, and the level of BRD4 expression was strongly related to poor prognosis. The BRD4-specific inhibitor JQ1 suppressed cell proliferation and colony formation and triggered cell apoptosis, cell cycle arrest, and changes in the expression of proteins in related signaling pathways. Moreover, JQ1 decreased the protein expression of BRD4 and c-Myc, and knockdown of BRD4 or c-Myc reduced the viability of EC cells. Intraperitoneal administration of JQ1 (50 mg/kg) significantly suppressed the tumorigenicity of EC cells in a xenograft mouse model. Conclusion Our results demonstrate that BRD4 is a potential marker of EC and that the BRD4 inhibitor JQ1 is a promising chemotherapeutic agent for the treatment of EC.

Objective To determine whether emodin facilitates the mesenchymal–epithelial transition (MET) of endometrial stromal cells (ESCs) as well as to explore the mechanism through which emodin favored the MET of ESCs. Methods Cell viability was tested by methyl thiazolyl tetrazolium assay. Cell migration and invasion abilities were detected by transwell assays. Levels of integrin-linked kinase (ILK) and epithelial–mesenchymal transition (EMT)-related proteins were detected by Western blot. Results Upregulated ILK and increased abilities of migration and invasion were confirmed in the eutopic and ectopic ESCs (EuSCs and EcSCs), especially in the EcSCs. After treated with emodin, the expression of ILK was statistically downregulated in EcSCs, resulting in the MET and decreased migration and invasion abilities of EcSCs. Additionally, silencing of the ILK gene in EcSCs also achieved the above-mentioned effects, which were strengthened by emodin. Furthermore, exogenous expression of ILK in control ESCs (CSCs) resulted in the EMT and increased abilities of migration and invasion of CSCs, which can be abrogated by emodin. Besides, exogenous expression of ILK also abrogated the effects of emodin on CSCs. Conclusion Emodin inhibits the migration and invasion abilities of human ESCs by facilitating the MET through targeting ILK.